Enrichment of endogenous fractalkine and anti-inflammatory cells via aptamer-functionalized hydrogels

Biomaterials. 2017 Oct;142:52-61. doi: 10.1016/j.biomaterials.2017.07.013. Epub 2017 Jul 10.

Abstract

Early recruitment of non-classical monocytes and their macrophage derivatives is associated with augmented tissue repair and improved integration of biomaterial constructs. A promising therapeutic approach to recruit these subpopulations is by elevating local concentrations of chemoattractants such as fractalkine (FKN, CX3CL1). However, delivering recombinant or purified proteins is not ideal due to their short half-lives, suboptimal efficacy, immunogenic potential, batch variabilities, and cost. Here we report an approach to enrich endogenous FKN, obviating the need for delivery of exogenous proteins. In this study, modified FKN-binding-aptamers are integrated with poly(ethylene glycol) diacrylate to form aptamer-functionalized hydrogels ("aptagels") that localize, dramatically enrich and passively release FKN in vitro for at least one week. Implantation in a mouse model of excisional skin injury demonstrates that aptagels enrich endogenous FKN and stimulate significant local increases in Ly6CloCX3CR1hi non-classical monocytes and CD206+ M2-like macrophages. The results demonstrate that orchestrators of inflammation can be manipulated without delivery of foreign proteins or cells and FKN-aptamer functionalized biomaterials may be a promising approach to recruit anti-inflammatory subpopulations to sites of injury. Aptagels are readily synthesized, highly customizable and could combine different aptamers to treat complex diseases in which regulation or enrichment of multiple proteins may be therapeutic.

Keywords: Aptamer; Endogenous; Fractalkine; Inflammation; Macrophage; Monocyte.

MeSH terms

  • Animals
  • Aptamers, Peptide / pharmacology*
  • CX3C Chemokine Receptor 1 / metabolism
  • Cell Movement / drug effects
  • Chemokine CX3CL1 / pharmacology*
  • Humans
  • Hydrogels / pharmacology*
  • Inflammation / pathology*
  • Kinetics
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Surface Plasmon Resonance
  • Time-Lapse Imaging

Substances

  • Aptamers, Peptide
  • CX3C Chemokine Receptor 1
  • Chemokine CX3CL1
  • Hydrogels
  • poly(ethylene glycol)diacrylate
  • Polyethylene Glycols